2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2006070806v1 18/1/255    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perianayagam, M. C. Articles by Jaber, B. L. Search for Related Content PubMed PubMed Citation Articles by Perianayagam, M. C. Articles by Jaber, B. L. Related Collections Related Article

NADPH Oxidase p22phox and Catalase Gene Variants Are Associated with Biomarkers of Oxidative Stress and Adverse Outcomes in Acute Renal Failure

Mary C. Perianayagam^*, Orfeas Liangos^*,, Alexey Y. Kolyada^*, Ron Wald, Robert W. MacKinnon^*, Lijun Li, Madhumati Rao, Vaidyanathapuram S. Balakrishnan, Joseph V. Bonventre, Brian J. Pereira and Bertrand L. Jaber^*,

^* Division of Nephrology, Kidney and Dialysis Research Laboratory, Caritas St. Elizabeth’s Medical Center, Division of Nephrology, Tufts-New England Medical Center, and Renal Division, Brigham and Women’s Hospital, Boston, Massachusetts

Address correspondence to: Dr. Bertrand L. Jaber, Department of Medicine, Caritas Street Elizabeth’s Medical Center, 736 Cambridge Street, Boston, MA 02135. Phone: 617-562-7832; Fax: 617-562-7797; E-mail: bertrand.jaber{at}caritaschristi.org

Received for publication July 30, 2006. Accepted for publication October 9, 2006.

Reactive oxygen species are important mediators of injury in acute renal failure (ARF). Although polymorphisms that affect key pro- and antioxidant enzymes might alter the susceptibility to oxidative stress–mediated injury, the use of genetic epidemiology for the study of oxidative stress–related genes has received little attention in ARF. The relationship of single-nucleotide polymorphisms in the coding region (C to T substitution at position +242) of the pro-oxidant enzyme NADPH oxidase p22phox subunit gene and in the promoter region (C to T substitution at position –262) of the antioxidant enzyme catalase gene to adverse clinical outcomes was evaluated prospectively in a cohort of 200 hospitalized patients with established ARF of mixed cause and severity. Genomic DNA was extracted from peripheral blood leukocytes and analyzed with a restriction fragment length polymorphism PCR method. Genotype–phenotype associations were characterized by measuring circulating nitrotyrosine and catalase activity. Observed and expected genotype frequencies were not significantly different, and overall baseline characteristics were not significantly different according to the various genotype groups. A genotype–phenotype association was demonstrable between the NADPH oxidase p22phox genotypes and plasma nitrotyrosine level (P = 0.06), as well as between the catalase genotypes and whole-blood catalase activity (P < 0.001). Compared with the NADPH oxidase p22phox CC genotype group, the T-allele group had a higher cumulative probability of remaining hospitalized (P = 0.03). Compared with the NADPH oxidase p22phox CC genotype, the T-allele carrier state was associated with 2.1-fold higher odds for dialysis requirement or hospital death (P = 0.01). This association persisted with 2.0- to 2.2-fold higher odds for this composite outcome after adjustment for race; gender; age; and the Acute Physiology and Chronic Health Evaluation II score (P = 0.03), the Multiple Organ Failure score (P = 0.01), or presence of sepsis (P = 0.02). The polymorphism in the gene that encodes the NADPH oxidase p22phox subunit at position +242 is associated with dialysis requirement or hospital death among patients with ARF. Larger studies are needed to confirm these relationships.

Related Article

Novel Approaches in the Investigation of Acute Kidney Injury

David P. Basile
J. Am. Soc. Nephrol. 2007 18: 7-9. [Full Text] [PDF]

This article has been cited by other articles:

				E. Fiaccadori, G. Regolisti, and A. Cabassi Specific nutritional problems in acute kidney injury, treated with non-dialysis and dialytic modalities NDT Plus, February 1, 2010; 3(1): 1 - 7. [Abstract] [Full Text] [PDF]

				J. C. T. Lu, S. G. Coca, U. D. Patel, L. Cantley, C. R. Parikh, and for the Translational Research Investigating Bioma Searching for Genes That Matter in Acute Kidney Injury: A Systematic Review Clin. J. Am. Soc. Nephrol., June 1, 2009; 4(6): 1020 - 1031. [Abstract] [Full Text] [PDF]

				V. Wizemann, P. Wabel, P. Chamney, W. Zaluska, U. Moissl, C. Rode, T. Malecka-Masalska, and D. Marcelli The mortality risk of overhydration in haemodialysis patients Nephrol. Dial. Transplant., May 1, 2009; 24(5): 1574 - 1579. [Abstract] [Full Text] [PDF]

				C. Hudson, J. Hudson, M. Swaminathan, A. Shaw, M. Stafford-Smith, and U. D. Patel Emerging Concepts in Acute Kidney Injury Following Cardiac Surgery Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2008; 12(4): 320 - 330. [Abstract] [PDF]

				A. L. Lagan, D. D. Melley, T. W. Evans, and G. J. Quinlan Pathogenesis of the systemic inflammatory syndrome and acute lung injury: role of iron mobilization and decompartmentalization Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L161 - L174. [Abstract] [Full Text] [PDF]

				D. P. Basile Novel Approaches in the Investigation of Acute Kidney Injury J. Am. Soc. Nephrol., January 1, 2007; 18(1): 7 - 9. [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673